title: Intestinal iron homeostasis and colon tumorigenesis.
abstract: Colorectal cancer (CRC) is the third most common cause of cancer-related deaths in industrialized countries. Understanding the mechanisms of growth and progression of CRC is essential to improve treatment. Iron is an essential nutrient for cell growth. Iron overload caused by hereditary mutations or excess dietary iron uptake has been identified as a risk factor for CRC. Intestinal iron is tightly controlled by iron transporters that are responsible for iron uptake, distribution, and export. Dysregulation of intestinal iron transporters are observed in CRC and lead to iron accumulation in tumors. Intratumoral iron results in oxidative stress, lipid peroxidation, protein modification and DNA damage with consequent promotion of oncogene activation. In addition, excess iron in intestinal tumors may lead to increase in tumor-elicited inflammation and tumor growth. Limiting intratumoral iron through specifically chelating excess intestinal iron or modulating activities of iron transporter may be an attractive therapeutic target for CRC.
authors.affiliation: Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA. xxue@umich.edu
authors.forename: Xiang
authors.initials: X
authors.lastname: Xue
authors.forename: Yatrik M
authors.initials: YM
authors.lastname: Shah
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000187:drug effects / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000209:etiology / Q000473:pathology; D004249:DNA Damage / Q000187:drug effects; D004195:Disease Models, Animal; D006706:Homeostasis; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D019190:Iron Overload / Q000378:metabolism; D019266:Iron, Dietary / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015227:Lipid Peroxidation / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D012307:Risk Factors
chemical_list: D019266:Iron, Dietary